Two billion persons, or about one third of the world's population, are estimated to be infected with the bacterium that causes tuberculosis (TB), a highly contagious disease that is one of the world's leading infectious causes of death. Between the years 2000 and 2020, it is estimated that one billion new TB infections will occur, resulting in 200 million people becoming sick and at least 35 million deaths (1).
Under the World Health Organization's (WHO's) current global TB control guidelines, smear microscopy testing of sputum samples of individuals exhibiting symptoms of the disease is used to identify patients as positive for acid-fast bacilli (AFB). If an individual tests positive for AFB, s/he meets the inclusion criteria for enrollment into WHO's “Direct Observation of Therapy Program” (DOTS). However, the reliability of smear microscopy test results, and other test modalities, depends on initially having good quality diagnostic samples on which to perform the test. A good quality sample is one containing an amount of sputum sufficient to detect the causative pathogen. Poor quality samples can directly impact the availability of WHO treatment protocol. A false-negative test result leads to denied treatment, and consequently, to the further spread of the disease.
The current case detection rate was most recently stated in the literature as 53 percent (2). A significant percentage of the missing cases may be due to false negative diagnoses resulting from testing specimens having amounts of sputum that are actually inadequate for such testing. Typically, a sputum sample is collected by means of the individual deeply inhaling and exhaling repeatedly, followed by coughing from as deep inside the chest as possible, thereby expectorating from the lungs or pulmonary passageways, into a collection container. However, often what is collected is mostly saliva, and the sample contains little or no real sputum. Although sputum can be thick and mucoid, it can also be fluid and similar in appearance to saliva. Thus, it is difficult to ascertain visually, at the time of collection, whether or not a collected sample is of sufficient quality, i.e., containing sufficient sputum, for AFB smear microscopy testing.
If a collected sample has an insufficient sputum concentration, it can yield a false-negative test result, and the patient would not be treated, and possibly would not be further observed. The patient may find it difficult to travel again to a medical center, and diagnosis may be delayed.
According to a 2003 epidemiological study (3) of TB, adverse outcomes of delay in initiating medical treatment include increased probability of death (4), increased risk of transmission to health care workers and others if the patient is hospitalized and not isolated (5), and increased transmission within the community (3).
In order to accurately diagnose TB, and promptly initiate both medical treatment and a rapid public health response, a test specimen of good quality must first be obtained from the individual. Currently, however, there is no practical method or device available, prior to laboratory testing for TB, to distinguish between usable sputum specimens and sub-standard specimens which are a source for false-negative AFB results. Clinical studies by Sloutsky (6) and others have shown that up to one-quarter or more of all TB sputum specimens collected may have limited diagnostic value because of the absence of adequate amounts of sputum in the sample, and that improvement in specimen quality can result in increased detection by as much as tens of percent (7).
Thus, there is an on-going clinical need for an improved method and apparatus to quickly identify, at the time a specimen is obtained from an individual, the suitability of the specimen for AFB smear microscopy testing. If such improved testing is available at the time of collection of a sample, a patient can be asked to remain long enough for the quality of the sample to be ascertained. If the sample is found to be unsuitable, the patient can provide another sample soon after.
There exists a need for an apparatus and a method of assessing specimen quality at the point of collection in order to enable the clinician to identify poor quality specimens and avoid submitting such specimens for diagnostic testing. Clinicians would be enabled to initially obtain better quality specimens, and to thereby maximize the rate of TB detection.
Another currently unmet need is a method of standardizing the diagnostic quality of clinical tuberculosis specimens. Yet another need is for a specimen collection and analysis device that can be conveniently handled so as to minimize the spread of infection during and subsequent to the specimen collection procedure.